Hypocholesterolemic activity of synthetic and natural tocotrienols.

Pearce, Bradley C.; Parker, Rex A.; Deason, M. E.; Qureshi, Asaf A.; Wright, John J.

doi:10.1021/jm00098a002

Cited by 264 publications

(177 citation statements)

References 3 publications

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“…T3 is claimed to be more active than T3 in inhibiting HMGCR, whereas T3 has a slight effect 14) . In contrast, TP induces HMGCR activity 15) .…”

Section: Introductionmentioning

confidence: 99%

Gamma Delta Tocotrienols Reduce Hepatic Triglyceride Synthesis and VLDL Secretion

Zaiden¹,

Yap²,

Ong³

et al. 2010

JAT

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Aim: Present study aimed to elucidate the suppression of serum lipids by gamma-and delta-tocotrienol ( T3).Methods: The lipid-lowering effects of T3 were investigated using HepG2 liver cell line, hypercholesterolemic mice and borderline-high cholesterol patients. Results:In-vitro results demonstrated two modes of action. First, T3 suppressed the upstream regulators of lipid homeostasis genes (DGAT2, APOB100, SREBP1/2 and HMGCR) leading to the suppression of triglycerides, cholesterol and VLDL biosyntheses. Second, T3 enhanced LDL efflux through induction of LDL receptor (LDLr) expression. Treatment of LDLr-deficient mice with 1 mg/day (50 mg/kg/day) T3 for one-month showed 28%, 19% reduction in cholesterol and triglyceride levels respectively, whereas HDL level was unaltered. The lipid-lowering effects were not affected by alpha-tocopherol ( TP). In a placebo-controlled human trial using 120 mg/day T3, only serum triglycerides were lowered by 28% followed by concomitant reduction in the triglyceriderich VLDL and chylomicrons. In contrast, total cholesterol, LDL and HDL remained unchanged in treated and placebo groups. The discrepancies between in-vitro, in-vivo and human studies may be attributed to the differential rates of post-absorptive T3 degradation and LDL metabolism. Conclusion: Reduction in triglycerides synthesis and transport may be the primary benefit caused by ingesting T3 in human.

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“…T3 is claimed to be more active than T3 in inhibiting HMGCR, whereas T3 has a slight effect 14) . In contrast, TP induces HMGCR activity 15) .…”

Section: Introductionmentioning

confidence: 99%

Gamma Delta Tocotrienols Reduce Hepatic Triglyceride Synthesis and VLDL Secretion

Zaiden¹,

Yap²,

Ong³

et al. 2010

JAT

View full text Add to dashboard Cite

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“…At concentrations of 25-50 M, ␣-tocopherol is known to regulate signal transduction pathways by mechanisms that are independent of its antioxidant properties (8,9). Micromolar amounts of tocotrienol, but not tocopherol, have been shown to suppress the activity of hydroxy-3-methylglutaryl-coenzyme A reductase (10,11). The unsaturated side chain of tocotrienol allows for more efficient penetration into tissues that have saturated fatty layers such as the brain and liver (12).…”

mentioning

confidence: 99%

Molecular Basis of Vitamin E Action

Khanna

Roy

Ryu

et al. 2003

Journal of Biological Chemistry

261

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Vitamin E is a generic term for tocopherols and tocotrienols. This work is based on our striking evidence that, in neuronal cells, nanomolar concentrations of ␣-tocotrienol, but not ␣-tocopherol, block glutamate-induced death by suppressing early activation of c-Src kinase (Sen, C. K., Khanna, S., Roy, S., and Packer, L. (2000) J. Biol. Chem. 275, 13049 -13055). This study on HT4 and immature primary cortical neurons suggests a central role of 12-lipoxygenase (12-LOX) in executing glutamate-induced neurodegeneration. BL15, an inhibitor of 12-LOX, prevented glutamate-induced neurotoxicity. Moreover, neurons isolated from 12-LOX-deficient mice were observed to be resistant to glutamate-induced death. In the presence of nanomolar ␣-tocotrienol, neurons were resistant to glutamate-, homocysteine-, and L-buthionine sulfoximine-induced toxicity. Long-term time-lapse imaging studies revealed that neurons and their axo-dendritic network are fairly motile under standard culture conditions. Such motility was arrested in response to glutamate challenge. Tocotrienol-treated primary neurons maintained healthy growth and motility even in the presence of excess glutamate. The study of 12-LOX activity and metabolism revealed that this key mediator of glutamate-induced neurodegeneration is subject to control by the nutrient ␣-tocotrienol. In silico docking studies indicated that ␣-tocotrienol may hinder the access of arachidonic acid to the catalytic site of 12-LOX by binding to the opening of a solvent cavity close to the active site. These findings lend further support to ␣-tocotrienol as a potent neuroprotective form of vitamin E.

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“…7 Micromolar amounts of tocotrienol suppress the activity of 3-Hydroxy-3-Methyl Glutaryl coenzyme A (HMG-CoA) reductase, the hepatic enzyme responsible for cholesterol synthesis. 11,12 Tocopherols do not share the cholesterol-lowering properties of tocotrienol.…”

Section: Functions and Health Effects Of Tocotrienolsmentioning

confidence: 99%

“…[8][9][10] Micromolar amounts of tocotrienol suppress the activity of 3-hydroxy -3-methyl glutaryl coenzyme A (HMG-CoA) reductase, the hepatic enzyme responsible for cholesterol biosynthesis. 11,12 In animal cells also T3 inthibitc production of cholesterol by liver cells by suppressing 3-Hydroxy 3-Methyl Glutaryl coA Reductase enzyme (HMGR), a key enzyme in the stereogenic pathway. 13 Tocopherols do not share the cholesterol properties of Tocotrienol.…”

Section: Introductionmentioning

confidence: 99%